Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation, jcm@btobioinnovation.com

Drugs at clinical stage

The US FDA Oncologic Drugs Advisory Committee (ODAC), with a vote 10-0, recommends the approval of Novartis' CTL019 or tisagentlecleucel, an investigational chimeric antigen receptor T cell (CAR-T) therapy as a treatment of relapsed or refractory (r:r) pediatric and yound adult patients with B-cell acute lymphoblastic leukemia (ALL).

If approved, later this year, the drug will be the first CAR-T cell therapy availablei in the world. CTL019 previously received US FDA Breakthrough Therapy designation and is still under Priority Review by the FDA

Acute lymphoblastic leukemia comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the USA. Effective treatment options for patients with r/r ALL are limited. In pediatric and young adult patients with B-cell ALL that have relapsed multiple times or become refractory to treatment, the five-year disease-free survival is less than 10-30%.

The highly personalized treatment CAR T-cell therapy is a type of cancer immunotherapyor that harnesses the body's immune system to take on cancer cells. CAR-T is manufactured for each individual patient using their own cells. During the treatment process, T cells are drawn from a patient's blood and reprogrammed in the manufacturing facility to create T cells that are genetically coded to express a chimeric antigen receptor to recognize and fight cancer cells and other B-cells expressing a specific antigen.

CTL019 was first developed by the University of Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of CTL019 after it is infused into the patient, which may be associated with long-lasting remissions in patients. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including CTL019, for the investigational treatment of cancers. Children's Hospital of Philadelphia was the first institution to investigate CTL019 in the treatment of pediatric patients and led the single site trial.

Other late stage CAR-T cell treatments are developed by Kite Pharma, Juno Therapeutics, Bluebird bio in collaboration with Celgene and Cellectis in collaboration with Servier and Pfizer.

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